US11406734B2 - Malleable demineralized bone composition and method of manufacture - Google Patents

Malleable demineralized bone composition and method of manufacture Download PDF

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US11406734B2
US11406734B2 US17/071,660 US202017071660A US11406734B2 US 11406734 B2 US11406734 B2 US 11406734B2 US 202017071660 A US202017071660 A US 202017071660A US 11406734 B2 US11406734 B2 US 11406734B2
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particles
freeze
dbm
cortical bone
gelatin
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US20210023271A1 (en
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Silvia Daniela Gonzales
Shabnam Namin
Timothy Ganey
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Vivex Biologics Group Inc
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/46Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2/4644Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/02Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/08Radiation
    • A61L2/087Particle radiation, e.g. electron-beam, alpha or beta radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222Gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3608Bone, e.g. demineralised bone matrix [DBM], bone powder
    • AHUMAN NECESSITIES
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    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3641Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
    • A61L27/3645Connective tissue
    • A61L27/365Bones
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    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3691Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • A61F2002/2817Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • A61F2002/2835Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0004Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/06Flowable or injectable implant compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/02Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • This invention is a malleable demineralized bone composition. More specifically, a composition that can be formed as a flowable paste or a molded shape retaining structure and a method of manufacture and use of said composition.
  • the present invention provides an improvement over those prior art materials.
  • a malleable demineralized bone composition consists of cortical bone made from a first portion and a second portion.
  • the first and second portions of cortical bone are made from cut pieces freeze dried then ground into particles and demineralized then freeze-dried.
  • a volume of the second portion is placed in a solution of sterile water to create a mixture, the water volume being seven times the second portion, the mixture is autoclaved under heat and pressure to form a gelatin, and the first portion is mixed with the gelatin to form a malleable putty or paste.
  • the freeze-dried DBM particles are ground to a particle size up to 300 microns.
  • the cut pieces having a width, a length and a thickness in the range of 1 to 4 mm, the pieces are freeze-dried and ground to form the cortical bone ground particles of the first portion that are less than 1000 microns and greater than 100 microns.
  • the ground particles are sieved to a first size range of 106 to 300 microns.
  • the malleable demineralized bone composition has a ratio of gelatin from the second portion to particles from the first portion of 80:20 by volume when mixed together.
  • the mixture forms a malleable putty or paste which can be packaged in a capped syringe.
  • the packaged mixture is stored at room temperature.
  • a method of making a malleable demineralized bone composition consisting of cortical bone comprises the steps of: preparing cortical bone by cutting the cortical bone into pieces, freeze-drying the pieces and then grinding into particles and demineralizing the ground particles and the freeze-drying the demineralized ground particles to form freeze-dried DBM particles; dividing the freeze-dried DBM particles into first and second portions wherein cortical bone plates are cut into long pieces, cleaned and then freeze-dried, grinding the freeze-dried pieces to obtain a particle size less than 300 microns and demineralizing the particles thereafter freeze-drying to form the freeze-dried DBM particles; autoclaving a volume of the second portion of DBM particles mixed with sterile water in a 7:1 ratio by volume for a predetermined time at a pre-set temperature and pressure to form a gelatin; cooling the gelatin made from the second portion; and mixing the freeze-dried ground particles of the first portion with the gelatin from the second portion at a ratio of 80:20 or
  • Cohesiveness is defined as the capacity of DBM aseptic paste to maintain its shape while immersed in normal saline or water for a minimum of one minute.
  • Cryopreserved Tissue frozen with the addition of, or in a solution containing, a cryoprotectant agent.
  • Freeze Dried/Lyophilized Tissue dehydrated for storage by conversion of the water content of frozen tissue to a gaseous state under vacuum that extracts moisture.
  • Malleability is the ability of DBM aseptic paste to be molded into different shapes with no visible cracks.
  • PBS Phosphate Buffered Saline
  • FIG. 1 shows a photograph of the malleable demineralized bone composition rolled into a “ball” like shape in the foreground and two composition filled syringes in the background.
  • FIG. 2 is a photograph of one composition filled syringe packaged in a clear sealed bag.
  • FIG. 3 is a schematic outline of the overall manufacture process.
  • FIG. 4 is the subprocess of cutting taken from FIG. 3 .
  • FIG. 5 is the subprocess of grinding and demineralizing taken from FIG. 3 .
  • FIG. 6 is the subprocess of gelatin preparation taken from FIG. 3 .
  • FIG. 7 is the subprocess of paste preparation taken from FIG. 3 .
  • FIG. 8 is the subprocess of packaging taken from FIG. 3 .
  • FIG. 9 is the subprocess of terminal sterilization using E-beam irradiation.
  • the present invention encompasses the manufacturing of a Demineralized Bone Matrix (DBM) aseptic paste or putty derived from human cadaveric cortical bone.
  • Cortical bone is obtained from male or female donors within suitable age groups. Full body donors with no joint replacements are preferred. The donors' medical and social history are screened for medical conditions such as osteoporosis and alcohol abuse, which may hinder the intended purpose of the final product.
  • the demineralization process of bone tissue exposes morphogenetic proteins and other intrinsic growth factors involved in providing the osteoinductive signal to form new bone. Therefore, the application of DBM aseptic paste products is intended to aid in the treatment of osseous defects and bone voids.
  • DBM aseptic paste or putty is ready for implantation and does not require preoperative preparation such as thawing or mixing. At room temperature, DBM aseptic paste or putty is moldable and cohesive.
  • the DBM paste or putty product is entirely derived from aseptic allograft cortical bone.
  • the cortical bone is aseptically cleaned, cut, morselized or shaved, ground, sieved at different sizes, demineralized and freeze dried to obtain cortical bone particles.
  • Gelatin is obtained from freeze dried ground cortical bone mixed with water.
  • DBM aseptic paste or putty is prepared by mixing ground cortical bone particles and gelatin.
  • final DBM aseptic paste or putty 10 products of 1, 5 or 10 cc are distributed into syringes 20 of 3 or 14 ml, packaged in final packaging 40 , as shown in FIG. 2 , and stored at room temperature until distribution to the end user.
  • FIG. 3 is an outline of the overall manufacturing process.
  • FIGS. 4-8 are each of the subprocesses.
  • the subprocess of cutting is schematically shown.
  • all extraneous material such as muscle fibers, adipose tissue, and periosteum are removed from the tissue.
  • Bones are then rinsed a minimum of 3 times with physiological grade normal saline (0.9% Sodium Chloride).
  • physiological grade normal saline (0.9% Sodium Chloride).
  • the bones are cut in a manner that the cortical and cancellous portions are separated.
  • Cortical bone shafts are cut in half longitudinally and placed in basins with normal saline. Further cleaning and cutting of cortical bone is divided into 2 subprocesses forming a first and second portion of the composition 10 , as detailed below.
  • Cortical bone bulk makes up the first portion 12 of the composition 10 .
  • Cortical bone plates are cut into small pieces using a band saw. The small pieces are rinsed a minimum of three times in normal saline and then placed into a metal container with normal saline. The container is wrapped, placed on a shaker and mechanically agitated for 5 to 10 minutes. The bone tissue is then morselized into 1 to 4 mm length and width pieces using a morselizer. The tissue is rinsed a minimum of three times with normal saline in order to remove any remnants of blood and/or fat deposits. The bone pieces are rinsed with hydrogen peroxide if required for no more than 10 minutes to remove fat/blood.
  • the bone pieces are rinsed a minimum of three times with sterile water to remove any residual hydrogen peroxide. Then, the bone tissue is placed in a metal cube, stored at ⁇ 80° C. and then freeze dried. The freeze drying cycle is set to run for 33 hours 50 minutes. It is understood the timing, ratios and volumes can vary based on the equipment and procedures used and the above is exemplary of the preferred process for the inventors' equipment.
  • Cortical bone bulk also makes up the second portion 14 of the composition 10 .
  • Cortical bone plates are cut into approximately 6.5 cm long pieces. The bone plates are placed in a wash can with normal saline. The wash can is wrapped and agitated for 5 to 10 minutes to remove any blood and adipose tissue. Bone tissues are then rinsed with normal saline as often as needed to clean tissue of blood and/or fatty deposits. The bone tissue pieces are collected in a basin and rinsed with hydrogen peroxide if required for no more than 10 minutes to remove fat/blood if necessary. Cortical bone particles are rinsed a minimum of three times with sterile water to remove any residual hydrogen peroxide. The particles are stored at ⁇ 80° C. and then freeze dried. The freeze drying cycle is set to run for 33 hours 50 minutes. It is understood the timing, ratios and volumes can vary based on the equipment and procedures used and the above is exemplary of the preferred process for the inventors' equipment.
  • the next subprocess is grinding-demineralization.
  • the particulate tissue After decanting the PBS, the particulate tissue is mixed with sterile water at a 20:1 ratio (20 ml of sterile water to 1 g of bone). The solution containing the tissue is placed on a magnetic stir plate for 9 minutes. The water waste solution is decanted and the demineralized particulate tissue is stored at ⁇ 80° C. The demineralized particulate tissue is freeze dried for 33 hours 50 minutes. At the end of the freeze drying process, a sample is collected for Residual Moisture testing.
  • the grinding-demineralization process of the first portion 12 of the composition 10 is similarly conducted.
  • Cortical bone mix once the freeze drying cycle is completed, the cortical bulk is ground and sieved to obtain particle sizes of 100 to 300 microns.
  • the mix of particulate tissue at different sizes is mixed with 0.7 HCL solution at a 20:1 ratio (20 ml of 0.7 HCL to 1 g of bone).
  • the solution containing the tissue is placed on a magnetic stir plate for 59 minutes.
  • the particulate tissue is mixed with sterile water at a 20:1 ratio (20 ml of sterile water to 1 g of bone).
  • the solution containing the tissue is placed on a magnetic stir plate for 4 minutes.
  • the process of decanting, mixing and incubating for 4 minutes is repeated with PBS solution.
  • the particulate tissue is mixed with sterile water at a 20:1 ratio (20 ml of sterile water to 1 g of bone).
  • the solution containing the tissue is placed on a magnetic stir plate for 9 minutes.
  • the water waste solution is decanted and the demineralized particulate tissue (DBM mix) is stored at ⁇ 80° C.
  • the DBM mix is freeze dried for 33 hours 50 minutes. At the end of the freeze drying process, samples are collected for residual moisture, residual calcium and osteoinduction testing.
  • the next subprocess, shown in FIG. 6 is gelatin preparation.
  • Gelatin preparation and DBM Aseptic Paste Preparation processes are contingent upon positive osteoinduction testing results of the DBM mix.
  • freeze-dried DBM particles are divided into groups of 100 cc, approximately. Each group is placed in a Pyrex glass bottle and mixed with sterile water. The ratio of sterile water to particles is 7:1 by volume. This ratio can be varied up or down by adjusting times to accommodate the altered ratios.
  • the mix is autoclaved for 1.25 hours.
  • the autoclaving process includes conditioning (15 minutes), exposure (30 minutes) and drying (30 minutes) steps. Temperature during the exposure step is 121.1° C. and the pressure is 30.15 psi. After autoclaving is completed, the gelatin is allowed to cool down to 37° C. in an incubator.
  • DBM aseptic paste preparation is described below.
  • DBM aseptic paste is prepared by mixing freeze-dried DBM mix with gelatin, which must not exceed 40° C. before mixing. The ratio of gelatin to DBM mix is 80:20 by volume, respectively.
  • the DBM paste is distributed into 3 ml or 14 ml syringes (1, 5 or 10 cc of product). The syringes are capped immediately after the DBM product is put in the syringe.
  • Surrogate samples of DBM aseptic paste are used for liquid culture sterility testing. Quality Control tests of malleability and cohesiveness are performed using a DBM aseptic paste sample after a minimum of 5 days of preparation.
  • Malleability is the ability of DBM aseptic paste to be molded into different shapes with no visible cracks. Cohesiveness is defined as the capacity of DBM aseptic paste to maintain its shape while immersed in normal saline or water for a minimum of one minute.
  • the subprocess shown in FIG. 8 is packaging. Capped syringes containing DBM aseptic paste products are packaged in validated final packaging. After final packaging, the product is terminally sterilized using E-beam irradiation as shown in FIG. 9 . The packaged final products are stored at room temperature until they are distributed to the end user.
  • bone particle sized and mixture can be employed depending on the application which, in this example, was bone regeneration. Lower volumes may be more suited for less intrusive bone repairs or more if larger if larger amounts of material are needed as in a hip defect or repair.
  • the exemplary process can be altered in terms of time, temperature, volume and material ratios and particle size distribution for a variety of adjustments to the paste or putty consistency.
  • the material achieved a low enough viscosity to be pushed through a syringe, but also can be made thick enough to retain its shape when molded like putty as the composition 10 in FIG. 1 shaped like a ball.

Abstract

A malleable demineralized bone composition consists of cortical bone made from a first portion and a second portion. The first portion and second portion of cortical bone is made from cut pieces freeze dried then ground into particles and demineralized then freeze-dried. A volume of the second portion is placed in a solution of sterile water to create a mixture, the water volume being seven times the volume of the second portion, the mixture is autoclaved under heat and pressure to form a gelatin, and the first portion is mixed with the gelatin to form a malleable putty or paste.

Description

RELATED APPLICATIONS
This application is a continuation of co-pending U.S. application Ser. No. 16/701,709 filed on Dec. 3, 2019 which is a continuation in part of U.S. application Ser. No. 15/136,301 filed Apr. 22, 2016, now U.S. Pat. No. 10,596,298 issued on Mar. 24, 2020 entitled, “Malleable Demineralized Bone Composition And Method Of Manufacture”.
TECHNICAL FIELD
This invention is a malleable demineralized bone composition. More specifically, a composition that can be formed as a flowable paste or a molded shape retaining structure and a method of manufacture and use of said composition.
BACKGROUND OF THE INVENTION
The manufacture and use of bone allografts from bone tissue is well known. The use of particles of various specific sizes and distributions have been determined to have beneficial characteristics for new bone growth in the treatment of osseous defects and bone voids.
The issue of getting the repair composition to stay in position has been addressed for various formulations made into malleable paste or putty by the addition of collagen or other gelatinous materials.
The present invention provides an improvement over those prior art materials.
SUMMARY OF THE INVENTION
A malleable demineralized bone composition consists of cortical bone made from a first portion and a second portion. The first and second portions of cortical bone are made from cut pieces freeze dried then ground into particles and demineralized then freeze-dried. A volume of the second portion is placed in a solution of sterile water to create a mixture, the water volume being seven times the second portion, the mixture is autoclaved under heat and pressure to form a gelatin, and the first portion is mixed with the gelatin to form a malleable putty or paste.
The freeze-dried DBM particles are ground to a particle size up to 300 microns. The cut pieces having a width, a length and a thickness in the range of 1 to 4 mm, the pieces are freeze-dried and ground to form the cortical bone ground particles of the first portion that are less than 1000 microns and greater than 100 microns. In a preferred embodiment, the ground particles are sieved to a first size range of 106 to 300 microns.
The malleable demineralized bone composition has a ratio of gelatin from the second portion to particles from the first portion of 80:20 by volume when mixed together. The mixture forms a malleable putty or paste which can be packaged in a capped syringe. The packaged mixture is stored at room temperature.
A method of making a malleable demineralized bone composition consisting of cortical bone comprises the steps of: preparing cortical bone by cutting the cortical bone into pieces, freeze-drying the pieces and then grinding into particles and demineralizing the ground particles and the freeze-drying the demineralized ground particles to form freeze-dried DBM particles; dividing the freeze-dried DBM particles into first and second portions wherein cortical bone plates are cut into long pieces, cleaned and then freeze-dried, grinding the freeze-dried pieces to obtain a particle size less than 300 microns and demineralizing the particles thereafter freeze-drying to form the freeze-dried DBM particles; autoclaving a volume of the second portion of DBM particles mixed with sterile water in a 7:1 ratio by volume for a predetermined time at a pre-set temperature and pressure to form a gelatin; cooling the gelatin made from the second portion; and mixing the freeze-dried ground particles of the first portion with the gelatin from the second portion at a ratio of 80:20 or less gelatin to DBM to create a malleable putty or paste.
Definitions
Cohesiveness is defined as the capacity of DBM aseptic paste to maintain its shape while immersed in normal saline or water for a minimum of one minute.
DBM—Demineralized Bone Matrix.
Cryopreserved—Tissue frozen with the addition of, or in a solution containing, a cryoprotectant agent.
Freeze Dried/Lyophilized—Tissue dehydrated for storage by conversion of the water content of frozen tissue to a gaseous state under vacuum that extracts moisture.
Malleability is the ability of DBM aseptic paste to be molded into different shapes with no visible cracks.
Normal Saline—0.9% Sodium Chloride Solution.
PBS—Phosphate Buffered Saline.
SRI—an equipment sterilization company.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be described by way of example and with reference to the accompanying drawings in which:
FIG. 1 shows a photograph of the malleable demineralized bone composition rolled into a “ball” like shape in the foreground and two composition filled syringes in the background.
FIG. 2 is a photograph of one composition filled syringe packaged in a clear sealed bag.
FIG. 3 is a schematic outline of the overall manufacture process.
FIG. 4 is the subprocess of cutting taken from FIG. 3.
FIG. 5 is the subprocess of grinding and demineralizing taken from FIG. 3.
FIG. 6 is the subprocess of gelatin preparation taken from FIG. 3.
FIG. 7 is the subprocess of paste preparation taken from FIG. 3.
FIG. 8 is the subprocess of packaging taken from FIG. 3.
FIG. 9 is the subprocess of terminal sterilization using E-beam irradiation.
DETAILED DESCRIPTION OF THE INVENTION
The present invention encompasses the manufacturing of a Demineralized Bone Matrix (DBM) aseptic paste or putty derived from human cadaveric cortical bone. Cortical bone is obtained from male or female donors within suitable age groups. Full body donors with no joint replacements are preferred. The donors' medical and social history are screened for medical conditions such as osteoporosis and alcohol abuse, which may hinder the intended purpose of the final product. The demineralization process of bone tissue exposes morphogenetic proteins and other intrinsic growth factors involved in providing the osteoinductive signal to form new bone. Therefore, the application of DBM aseptic paste products is intended to aid in the treatment of osseous defects and bone voids. DBM aseptic paste or putty is ready for implantation and does not require preoperative preparation such as thawing or mixing. At room temperature, DBM aseptic paste or putty is moldable and cohesive.
The DBM paste or putty product is entirely derived from aseptic allograft cortical bone. The cortical bone is aseptically cleaned, cut, morselized or shaved, ground, sieved at different sizes, demineralized and freeze dried to obtain cortical bone particles. Gelatin is obtained from freeze dried ground cortical bone mixed with water. DBM aseptic paste or putty is prepared by mixing ground cortical bone particles and gelatin. As shown in FIG. 1, final DBM aseptic paste or putty 10 products of 1, 5 or 10 cc are distributed into syringes 20 of 3 or 14 ml, packaged in final packaging 40, as shown in FIG. 2, and stored at room temperature until distribution to the end user. To ensure the osteoinductive potential of the final product, every lot of demineralized particulate tissue used to prepare DBM aseptic paste is tested in vitro using the C2C12 differentiation assay, which has been shown to have a positive correlation with results obtained in vivo.
FIG. 3 is an outline of the overall manufacturing process. FIGS. 4-8 are each of the subprocesses.
With reference to FIG. 4, the subprocess of cutting is schematically shown. Prior to cutting the donated and approved for processing aseptic human cadaveric cortical bone, all extraneous material such as muscle fibers, adipose tissue, and periosteum are removed from the tissue. Bones are then rinsed a minimum of 3 times with physiological grade normal saline (0.9% Sodium Chloride). Using a band saw, the bones are cut in a manner that the cortical and cancellous portions are separated. Cortical bone shafts are cut in half longitudinally and placed in basins with normal saline. Further cleaning and cutting of cortical bone is divided into 2 subprocesses forming a first and second portion of the composition 10, as detailed below.
Cortical bone bulk makes up the first portion 12 of the composition 10. Cortical bone plates are cut into small pieces using a band saw. The small pieces are rinsed a minimum of three times in normal saline and then placed into a metal container with normal saline. The container is wrapped, placed on a shaker and mechanically agitated for 5 to 10 minutes. The bone tissue is then morselized into 1 to 4 mm length and width pieces using a morselizer. The tissue is rinsed a minimum of three times with normal saline in order to remove any remnants of blood and/or fat deposits. The bone pieces are rinsed with hydrogen peroxide if required for no more than 10 minutes to remove fat/blood. The bone pieces are rinsed a minimum of three times with sterile water to remove any residual hydrogen peroxide. Then, the bone tissue is placed in a metal cube, stored at −80° C. and then freeze dried. The freeze drying cycle is set to run for 33 hours 50 minutes. It is understood the timing, ratios and volumes can vary based on the equipment and procedures used and the above is exemplary of the preferred process for the inventors' equipment.
Cortical bone bulk also makes up the second portion 14 of the composition 10. Cortical bone plates are cut into approximately 6.5 cm long pieces. The bone plates are placed in a wash can with normal saline. The wash can is wrapped and agitated for 5 to 10 minutes to remove any blood and adipose tissue. Bone tissues are then rinsed with normal saline as often as needed to clean tissue of blood and/or fatty deposits. The bone tissue pieces are collected in a basin and rinsed with hydrogen peroxide if required for no more than 10 minutes to remove fat/blood if necessary. Cortical bone particles are rinsed a minimum of three times with sterile water to remove any residual hydrogen peroxide. The particles are stored at −80° C. and then freeze dried. The freeze drying cycle is set to run for 33 hours 50 minutes. It is understood the timing, ratios and volumes can vary based on the equipment and procedures used and the above is exemplary of the preferred process for the inventors' equipment.
As shown in FIG. 5, the next subprocess is grinding-demineralization.
Further processing of cortical bone is detailed below.
The cortical bone bulk pieces; once the freeze drying cycle is completed, the cortical bone bulk pieces are ground and sieved to obtain particle sizes of 106 to 300 μM. Then, the particulate tissue is mixed with 0.6 HCL solution at a 20:1 ratio (20 ml of 0.6 HCL to 1 g of bone). The solution containing the tissue is placed on a magnetic stir plate for 19 minutes. After decanting the liquid, the particulate tissue is mixed with sterile water at a 20:1 ratio (20 ml of sterile water to 1 g of bone). The solution containing the tissue is placed on a magnetic stir plate for 4 minutes. The process of decanting, mixing and incubating for 4 minutes is repeated with PBS solution. After decanting the PBS, the particulate tissue is mixed with sterile water at a 20:1 ratio (20 ml of sterile water to 1 g of bone). The solution containing the tissue is placed on a magnetic stir plate for 9 minutes. The water waste solution is decanted and the demineralized particulate tissue is stored at −80° C. The demineralized particulate tissue is freeze dried for 33 hours 50 minutes. At the end of the freeze drying process, a sample is collected for Residual Moisture testing.
The grinding-demineralization process of the first portion 12 of the composition 10 is similarly conducted. Cortical bone mix; once the freeze drying cycle is completed, the cortical bulk is ground and sieved to obtain particle sizes of 100 to 300 microns. Then, the mix of particulate tissue at different sizes is mixed with 0.7 HCL solution at a 20:1 ratio (20 ml of 0.7 HCL to 1 g of bone). The solution containing the tissue is placed on a magnetic stir plate for 59 minutes. After decanting the liquid, the particulate tissue is mixed with sterile water at a 20:1 ratio (20 ml of sterile water to 1 g of bone). The solution containing the tissue is placed on a magnetic stir plate for 4 minutes. The process of decanting, mixing and incubating for 4 minutes is repeated with PBS solution. After decanting the PBS, the particulate tissue is mixed with sterile water at a 20:1 ratio (20 ml of sterile water to 1 g of bone). The solution containing the tissue is placed on a magnetic stir plate for 9 minutes. The water waste solution is decanted and the demineralized particulate tissue (DBM mix) is stored at −80° C. The DBM mix is freeze dried for 33 hours 50 minutes. At the end of the freeze drying process, samples are collected for residual moisture, residual calcium and osteoinduction testing.
The next subprocess, shown in FIG. 6, is gelatin preparation. Gelatin preparation and DBM Aseptic Paste Preparation processes are contingent upon positive osteoinduction testing results of the DBM mix. For gelatin preparation, freeze-dried DBM particles are divided into groups of 100 cc, approximately. Each group is placed in a Pyrex glass bottle and mixed with sterile water. The ratio of sterile water to particles is 7:1 by volume. This ratio can be varied up or down by adjusting times to accommodate the altered ratios. In order to prepare gelatin, the mix is autoclaved for 1.25 hours. The autoclaving process includes conditioning (15 minutes), exposure (30 minutes) and drying (30 minutes) steps. Temperature during the exposure step is 121.1° C. and the pressure is 30.15 psi. After autoclaving is completed, the gelatin is allowed to cool down to 37° C. in an incubator.
As shown in FIG. 7, DBM aseptic paste preparation is described below.
DBM aseptic paste is prepared by mixing freeze-dried DBM mix with gelatin, which must not exceed 40° C. before mixing. The ratio of gelatin to DBM mix is 80:20 by volume, respectively. The DBM paste is distributed into 3 ml or 14 ml syringes (1, 5 or 10 cc of product). The syringes are capped immediately after the DBM product is put in the syringe. Surrogate samples of DBM aseptic paste are used for liquid culture sterility testing. Quality Control tests of malleability and cohesiveness are performed using a DBM aseptic paste sample after a minimum of 5 days of preparation. Malleability is the ability of DBM aseptic paste to be molded into different shapes with no visible cracks. Cohesiveness is defined as the capacity of DBM aseptic paste to maintain its shape while immersed in normal saline or water for a minimum of one minute.
The subprocess shown in FIG. 8 is packaging. Capped syringes containing DBM aseptic paste products are packaged in validated final packaging. After final packaging, the product is terminally sterilized using E-beam irradiation as shown in FIG. 9. The packaged final products are stored at room temperature until they are distributed to the end user.
Other ranges of bone particle sized and mixture can be employed depending on the application which, in this example, was bone regeneration. Lower volumes may be more suited for less intrusive bone repairs or more if larger if larger amounts of material are needed as in a hip defect or repair.
It is understood, the exemplary process can be altered in terms of time, temperature, volume and material ratios and particle size distribution for a variety of adjustments to the paste or putty consistency. Ideally, the material achieved a low enough viscosity to be pushed through a syringe, but also can be made thick enough to retain its shape when molded like putty as the composition 10 in FIG. 1 shaped like a ball.
Variations in the present invention are possible in light of the description of it provided herein. While certain representative embodiments and details have been shown for the purpose of illustrating the subject invention, it will be apparent to those skilled in this art that various changes and modifications can be made therein without departing from the scope of the subject invention. It is, therefore, to be understood that changes can be made in the particular embodiments described, which will be within the full intended scope of the invention as defined by the following appended claims.

Claims (2)

What is claimed is:
1. A method of making a malleable demineralized bone composition consisting of cortical bone, comprising the steps of
a) preparing cortical bone by cutting the cortical bone into pieces, freeze-drying the pieces and then grinding into particles and demineralizing the ground particles and freeze-drying the demineralized ground particles to form freeze-dried demineralized bone matrix (DBM) particles;
b) dividing the freeze-dried DBM particles into a first portion and a second portion;
c) autoclaving a volume of the second portion of DBM particles mixed with sterile water to form a gelatin;
d) cooling the gelatin; and
e) mixing the freeze-dried ground particles of the first portion with the gelatin from the second portion at a ratio of 80:20 or less gelatin to DBM to create a malleable and cohesive putty or paste, wherein the malleable and cohesive putty or paste is moldable into different shapes with no visible cracks and maintains its shape while immersed in normal saline or water for a minimum of one minute.
2. A method of making a malleable demineralized bone composition consisting of cortical bone comprising:
a) preparing a first portion of cortical bone by cutting the cortical bone into pieces, freeze-drying the pieces and then grinding into particles and demineralizing the ground particles and thereafter freeze-drying the demineralized ground particles to form a first portion of demineralized bone matrix (DBM) particles;
b) preparing a second portion of cortical bone by shaving cortical bone plates cut into 6.5 cm long pieces, wherein cortical bone is cut into long pieces from the cortical bone plates, cleaned and then shaved to form shavings of cortical bone tissue then freeze-drying the shavings, grinding the freeze-dried shavings to obtain a particle size less than 150 μm, and demineralizing the particles thereafter freeze-drying to form a second portion of DBM particles;
c) autoclaving a volume of the second portion of DBM particles mixed with sterile water to form a gelatin;
d) cooling the gelatin made from the second portion; and
e) mixing the freeze-dried ground particles of the first portion with the gelatin from the second portion at a ratio of 80:20 or less gelatin to DBM to create a malleable and cohesive putty or paste, wherein the malleable and cohesive putty or paste is moldable into different shapes with no visible cracks and maintains its shape while immersed in normal saline or water for a minimum of one minute.
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Publication number Priority date Publication date Assignee Title
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Citations (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3458397A (en) 1966-12-08 1969-07-29 Squibb & Sons Inc Process for producing osteogenic material
US4172128A (en) 1975-03-26 1979-10-23 Erhard Thiele Process of degrading and regenerating bone and tooth material and products
US4440750A (en) 1982-02-12 1984-04-03 Collagen Corporation Osteogenic composition and method
US5073373A (en) 1989-09-21 1991-12-17 Osteotech, Inc. Flowable demineralized bone powder composition and its use in bone repair
US5236456A (en) 1989-11-09 1993-08-17 Osteotech, Inc. Osteogenic composition and implant containing same
US5486359A (en) 1990-11-16 1996-01-23 Osiris Therapeutics, Inc. Human mesenchymal stem cells
US5490937A (en) 1990-09-17 1996-02-13 Genentech, Inc. Tangential flow filtration process and apparatus
US5531791A (en) 1993-07-23 1996-07-02 Bioscience Consultants Composition for repair of defects in osseous tissues, method of making, and prosthesis
US5733542A (en) 1990-11-16 1998-03-31 Haynesworth; Stephen E. Enhancing bone marrow engraftment using MSCS
WO1999038543A2 (en) * 1998-01-28 1999-08-05 Regeneration Technologies, Inc. Bone paste subjected to irradiative and thermal treatment
US6432436B1 (en) 2000-10-03 2002-08-13 Musculoskeletal Transplant Foundation Partially demineralized cortical bone constructs
US6437018B1 (en) 1998-02-27 2002-08-20 Musculoskeletal Transplant Foundation Malleable paste with high molecular weight buffered carrier for filling bone defects
US6458375B1 (en) 1998-02-27 2002-10-01 Musculoskeletal Transplant Foundation Malleable paste with allograft bone reinforcement for filling bone defects
US20020192266A1 (en) 2001-05-21 2002-12-19 Miles Douglas C. Therapeutic and nutritive dietary composition and method of use
US20030059414A1 (en) 2001-09-21 2003-03-27 Ho Tony W. Cell populations which co-express CD49c and CD90
US6576249B1 (en) 2000-11-13 2003-06-10 El Gendler Bone putty and method
US20040058412A1 (en) 2002-09-20 2004-03-25 Neuronyx, Inc. Cell populations which co-express CD49c and CD90
US20040097612A1 (en) 2002-11-15 2004-05-20 Etex Corporation Cohesive demineralized bone compositions
USRE38522E1 (en) 1998-02-27 2004-05-25 Musculoskeletal Transplant Foundation Malleable paste for filling bone defects
US6911212B2 (en) 1998-02-27 2005-06-28 Musculoskeletal Transplant Foundation Malleable putty and flowable paste with allograft bone having residual calcium for filling bone defects
US20050181502A1 (en) 1999-08-05 2005-08-18 Athersys, Inc. Multipotent adult stem cells and methods for isolation
US20060004189A1 (en) 2004-07-02 2006-01-05 James Gandy Compositions for treating wounds and processes for their preparation
US6998135B1 (en) 1998-02-27 2006-02-14 Musculoskeletal Transplant Foundation Demineralized corticocancellous bone sheet
US7019192B2 (en) 1998-02-27 2006-03-28 Musculoskeletal Transplant Foundation Composition for filling bone defects
US20060083769A1 (en) * 2004-10-14 2006-04-20 Mukesh Kumar Method and apparatus for preparing bone
US7045141B2 (en) 1998-02-27 2006-05-16 Musculoskeletal Transplant Foundation Allograft bone composition having a gelatin binder
US7067123B2 (en) 2003-04-29 2006-06-27 Musculoskeletal Transplant Foundation Glue for cartilage repair
US20060204544A1 (en) * 2002-05-20 2006-09-14 Musculoskeletal Transplant Foundation Allograft bone composition having a gelatin binder
US20060280803A1 (en) * 2004-10-14 2006-12-14 Mukesh Kumar Method and apparatus for repairing bone
US20070049739A1 (en) 2005-08-30 2007-03-01 Biomet Manufacturing Corp. Method and system for extracting blood-derived growth factors
US20070052417A1 (en) 2005-09-02 2007-03-08 Toshiba America Mri, Inc. Method and apparatus for diffusion magnetic resonance imaging with the effects of eddy currents compensated
USRE39587E1 (en) 1998-02-27 2007-04-24 Musculoskeletal Transplant Foundation Malleable paste for filling bone defects
US20080281431A1 (en) * 2007-05-10 2008-11-13 Biomet Manufacturing Corp. Resorbable bone graft materials
US7488348B2 (en) 2003-05-16 2009-02-10 Musculoskeletal Transplant Foundation Cartilage allograft plug
US20090227704A1 (en) * 2008-03-05 2009-09-10 Karen Troxel Cohesive and compression resistant demineralized bone carrier matrix
US7824702B2 (en) 1999-12-29 2010-11-02 Rti Biologics, Inc. Composition for making a bone paste
US7847072B2 (en) 2002-06-26 2010-12-07 Zimmer Orthobiologics, Inc. Rapid isolation of osteoinductive protein mixtures from mammalian bone tissue
US7879103B2 (en) 2005-04-15 2011-02-01 Musculoskeletal Transplant Foundation Vertebral disc repair
US7901457B2 (en) 2003-05-16 2011-03-08 Musculoskeletal Transplant Foundation Cartilage allograft plug
US8075881B2 (en) 1999-08-05 2011-12-13 Regents Of The University Of Minnesota Use of multipotent adult stem cells in treatment of myocardial infarction and congestive heart failure
US20120121660A1 (en) * 2010-11-15 2012-05-17 Zimmer Orthobiologics, Inc. Bone void fillers
US8202539B2 (en) * 2007-10-19 2012-06-19 Warsaw Orthopedic, Inc. Demineralized bone matrix compositions and methods
US8292968B2 (en) 2004-10-12 2012-10-23 Musculoskeletal Transplant Foundation Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles
US8354370B2 (en) 2007-06-15 2013-01-15 Garnet Biotherapeutics, Inc. Administering a biological composition or compositions isolated from self-renewing colony forming somatic cell growth medium to treat diseases and disorders
US8357384B2 (en) * 2007-06-15 2013-01-22 Warsaw Orthopedic, Inc. Bone matrix compositions and methods
US8394419B2 (en) 2006-02-27 2013-03-12 Global Medical, Inc. Bone graft materials derived from mineralized gelatin
US20130195810A1 (en) 2007-05-03 2013-08-01 The Brigham And Women's Hospital, Inc. Multipotent stem cells and uses thereof
US20140005793A1 (en) 2012-06-21 2014-01-02 Keith Cameron Koford Novel biological implant compositions, implants and methods
US20140010890A1 (en) * 2006-02-27 2014-01-09 Globus Medical, Inc. Bone Graft Materials Derived from Mineralized Gelatin
US20140030235A1 (en) 2006-01-12 2014-01-30 Osiris Therapeutics, Inc. Use of Mesenchymal Stem Cells for Treating Genetic Disease and Disorders
US8834928B1 (en) 2011-05-16 2014-09-16 Musculoskeletal Transplant Foundation Tissue-derived tissugenic implants, and methods of fabricating and using same
US9138509B2 (en) 2007-09-14 2015-09-22 Musculoskeletal Transplant Foundation Composition for filling bone defects
US9192695B2 (en) 2008-11-20 2015-11-24 Allosource Allografts combined with tissue derived stem cells for bone healing
US20160296668A1 (en) 2013-10-08 2016-10-13 Vivorte, Inc.. Processed bone particle compositions and related methods
US9554920B2 (en) * 2007-06-15 2017-01-31 Warsaw Orthopedic, Inc. Bone matrix compositions having nanoscale textured surfaces
US10123876B2 (en) * 2016-04-22 2018-11-13 Vivex Biomedical, Inc. Cohesive bone composition
US10357593B2 (en) * 2016-04-22 2019-07-23 Vivex Biomedical, Inc. Malleable demineralized bone composition and method of manufacture
US20200101197A1 (en) * 2016-04-22 2020-04-02 Vivex Biologics Group, Inc. Malleable demineralized bone composition and method of manufacture

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7744597B2 (en) * 2002-06-26 2010-06-29 Lifenet Health Device and process for producing fiber products and fiber products produced thereby
US9913676B2 (en) * 2014-11-14 2018-03-13 Warsaw Orthopedic, Inc. Milled bone graft materials and methods of use
EP3256070A4 (en) * 2015-02-10 2018-10-17 Lifenet Health Biologically functional soft tissue scaffolds and implants
AU2017254618B2 (en) * 2016-04-19 2021-04-01 Warsaw Orthopedic, Inc. An implantable composite containing carbonated hydroxyapatite

Patent Citations (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3458397A (en) 1966-12-08 1969-07-29 Squibb & Sons Inc Process for producing osteogenic material
US4172128A (en) 1975-03-26 1979-10-23 Erhard Thiele Process of degrading and regenerating bone and tooth material and products
US4440750A (en) 1982-02-12 1984-04-03 Collagen Corporation Osteogenic composition and method
US5073373A (en) 1989-09-21 1991-12-17 Osteotech, Inc. Flowable demineralized bone powder composition and its use in bone repair
US5236456A (en) 1989-11-09 1993-08-17 Osteotech, Inc. Osteogenic composition and implant containing same
US5490937A (en) 1990-09-17 1996-02-13 Genentech, Inc. Tangential flow filtration process and apparatus
US5486359A (en) 1990-11-16 1996-01-23 Osiris Therapeutics, Inc. Human mesenchymal stem cells
US5733542A (en) 1990-11-16 1998-03-31 Haynesworth; Stephen E. Enhancing bone marrow engraftment using MSCS
US5531791A (en) 1993-07-23 1996-07-02 Bioscience Consultants Composition for repair of defects in osseous tissues, method of making, and prosthesis
WO1999038543A2 (en) * 1998-01-28 1999-08-05 Regeneration Technologies, Inc. Bone paste subjected to irradiative and thermal treatment
USRE39587E1 (en) 1998-02-27 2007-04-24 Musculoskeletal Transplant Foundation Malleable paste for filling bone defects
US6437018B1 (en) 1998-02-27 2002-08-20 Musculoskeletal Transplant Foundation Malleable paste with high molecular weight buffered carrier for filling bone defects
US6458375B1 (en) 1998-02-27 2002-10-01 Musculoskeletal Transplant Foundation Malleable paste with allograft bone reinforcement for filling bone defects
US7045141B2 (en) 1998-02-27 2006-05-16 Musculoskeletal Transplant Foundation Allograft bone composition having a gelatin binder
USRE38522E1 (en) 1998-02-27 2004-05-25 Musculoskeletal Transplant Foundation Malleable paste for filling bone defects
US6911212B2 (en) 1998-02-27 2005-06-28 Musculoskeletal Transplant Foundation Malleable putty and flowable paste with allograft bone having residual calcium for filling bone defects
US7019192B2 (en) 1998-02-27 2006-03-28 Musculoskeletal Transplant Foundation Composition for filling bone defects
US6998135B1 (en) 1998-02-27 2006-02-14 Musculoskeletal Transplant Foundation Demineralized corticocancellous bone sheet
US7659118B2 (en) 1999-08-05 2010-02-09 Abt Holding Company Multipotent adult stem cells
US7015037B1 (en) 1999-08-05 2006-03-21 Regents Of The University Of Minnesota Multiponent adult stem cells and methods for isolation
US8075881B2 (en) 1999-08-05 2011-12-13 Regents Of The University Of Minnesota Use of multipotent adult stem cells in treatment of myocardial infarction and congestive heart failure
US20050181502A1 (en) 1999-08-05 2005-08-18 Athersys, Inc. Multipotent adult stem cells and methods for isolation
US7824702B2 (en) 1999-12-29 2010-11-02 Rti Biologics, Inc. Composition for making a bone paste
US6432436B1 (en) 2000-10-03 2002-08-13 Musculoskeletal Transplant Foundation Partially demineralized cortical bone constructs
US6576249B1 (en) 2000-11-13 2003-06-10 El Gendler Bone putty and method
US20020192266A1 (en) 2001-05-21 2002-12-19 Miles Douglas C. Therapeutic and nutritive dietary composition and method of use
US20030059414A1 (en) 2001-09-21 2003-03-27 Ho Tony W. Cell populations which co-express CD49c and CD90
US20060204544A1 (en) * 2002-05-20 2006-09-14 Musculoskeletal Transplant Foundation Allograft bone composition having a gelatin binder
US7847072B2 (en) 2002-06-26 2010-12-07 Zimmer Orthobiologics, Inc. Rapid isolation of osteoinductive protein mixtures from mammalian bone tissue
US20040058412A1 (en) 2002-09-20 2004-03-25 Neuronyx, Inc. Cell populations which co-express CD49c and CD90
US20040097612A1 (en) 2002-11-15 2004-05-20 Etex Corporation Cohesive demineralized bone compositions
US7067123B2 (en) 2003-04-29 2006-06-27 Musculoskeletal Transplant Foundation Glue for cartilage repair
USRE43258E1 (en) 2003-04-29 2012-03-20 Musculoskeletal Transplant Foundation Glue for cartilage repair
USRE42208E1 (en) 2003-04-29 2011-03-08 Musculoskeletal Transplant Foundation Glue for cartilage repair
US8221500B2 (en) 2003-05-16 2012-07-17 Musculoskeletal Transplant Foundation Cartilage allograft plug
US7488348B2 (en) 2003-05-16 2009-02-10 Musculoskeletal Transplant Foundation Cartilage allograft plug
US7901457B2 (en) 2003-05-16 2011-03-08 Musculoskeletal Transplant Foundation Cartilage allograft plug
US20060004189A1 (en) 2004-07-02 2006-01-05 James Gandy Compositions for treating wounds and processes for their preparation
US8292968B2 (en) 2004-10-12 2012-10-23 Musculoskeletal Transplant Foundation Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles
US20060083769A1 (en) * 2004-10-14 2006-04-20 Mukesh Kumar Method and apparatus for preparing bone
US20060280803A1 (en) * 2004-10-14 2006-12-14 Mukesh Kumar Method and apparatus for repairing bone
US7879103B2 (en) 2005-04-15 2011-02-01 Musculoskeletal Transplant Foundation Vertebral disc repair
US20070049739A1 (en) 2005-08-30 2007-03-01 Biomet Manufacturing Corp. Method and system for extracting blood-derived growth factors
US20070052417A1 (en) 2005-09-02 2007-03-08 Toshiba America Mri, Inc. Method and apparatus for diffusion magnetic resonance imaging with the effects of eddy currents compensated
US20140030235A1 (en) 2006-01-12 2014-01-30 Osiris Therapeutics, Inc. Use of Mesenchymal Stem Cells for Treating Genetic Disease and Disorders
US8394419B2 (en) 2006-02-27 2013-03-12 Global Medical, Inc. Bone graft materials derived from mineralized gelatin
US9138508B2 (en) 2006-02-27 2015-09-22 Globus Medical, Inc. Bone graft materials derived from mineralized gelatin
US20140010890A1 (en) * 2006-02-27 2014-01-09 Globus Medical, Inc. Bone Graft Materials Derived from Mineralized Gelatin
US20130195810A1 (en) 2007-05-03 2013-08-01 The Brigham And Women's Hospital, Inc. Multipotent stem cells and uses thereof
US20080281431A1 (en) * 2007-05-10 2008-11-13 Biomet Manufacturing Corp. Resorbable bone graft materials
US8357384B2 (en) * 2007-06-15 2013-01-22 Warsaw Orthopedic, Inc. Bone matrix compositions and methods
US9554920B2 (en) * 2007-06-15 2017-01-31 Warsaw Orthopedic, Inc. Bone matrix compositions having nanoscale textured surfaces
US8354370B2 (en) 2007-06-15 2013-01-15 Garnet Biotherapeutics, Inc. Administering a biological composition or compositions isolated from self-renewing colony forming somatic cell growth medium to treat diseases and disorders
US9138509B2 (en) 2007-09-14 2015-09-22 Musculoskeletal Transplant Foundation Composition for filling bone defects
US8202539B2 (en) * 2007-10-19 2012-06-19 Warsaw Orthopedic, Inc. Demineralized bone matrix compositions and methods
US20090227704A1 (en) * 2008-03-05 2009-09-10 Karen Troxel Cohesive and compression resistant demineralized bone carrier matrix
US9192695B2 (en) 2008-11-20 2015-11-24 Allosource Allografts combined with tissue derived stem cells for bone healing
US20160030639A1 (en) 2008-11-20 2016-02-04 Allosource Allografts Combined with Tissue Derived Stem Cells For Bone Healing
US20120121660A1 (en) * 2010-11-15 2012-05-17 Zimmer Orthobiologics, Inc. Bone void fillers
US8834928B1 (en) 2011-05-16 2014-09-16 Musculoskeletal Transplant Foundation Tissue-derived tissugenic implants, and methods of fabricating and using same
US20150012107A1 (en) 2012-06-21 2015-01-08 RIT Surgical, Inc. Novel biological implant compositions, implants and methods
US20140005793A1 (en) 2012-06-21 2014-01-02 Keith Cameron Koford Novel biological implant compositions, implants and methods
US20160296668A1 (en) 2013-10-08 2016-10-13 Vivorte, Inc.. Processed bone particle compositions and related methods
US10123876B2 (en) * 2016-04-22 2018-11-13 Vivex Biomedical, Inc. Cohesive bone composition
US10357593B2 (en) * 2016-04-22 2019-07-23 Vivex Biomedical, Inc. Malleable demineralized bone composition and method of manufacture
US20200101197A1 (en) * 2016-04-22 2020-04-02 Vivex Biologics Group, Inc. Malleable demineralized bone composition and method of manufacture

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Chu Chang Chua, Deborah Ceiman, and Roger L. Ladda; "Transforming Growth Factors Released From Kirsten Sarcoma Virus Transformed Cells Do Not Compete for Epidermal Growth Factor Membrane Receptors"; Journal of Cellular Physiology 117:116-122 (1983).
Osteocel bone graft web page, http://www.nuvasive.com/patient-solutions/nuvasive-integrated-surgical-solutions/osteocel-bone-graft/; 2016.
Trinity Elite, product, sales brochure, TT-1515, Orthofix Holdings Inc, Oct. 2015.
Yawei Liu,A, Anders Kalenb, Olof Ristob & ; "Time- and pH-dependent release of PDGF and TGF-ß from platelets&It;emph type="2">in vitro&It;/emph>"; pp. 233-237 Platelets vol. 14, Issue 4, 2003 ; Published online: Jul. 7, 2009.
Yawei Liu,A, Anders Kalenb, Olof Ristob & ; "Time- and pH-dependent release of PDGF and TGF-ß from platelets&It;emph type="2">in vitro&It;/emph>"; pp. 233-237 Platelets vol. 14, Issue 4, 2003 ; Published online: Jul. 7, 2009.

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